This research will continue the development of a prototype emission-transmission computed tomographic (ETCT) scanner for simultaneous acquisition of dual-energy x-ray CT and emissionradionuclide CT. The transmission and emission data are acquired simultaneously with a single high-purity germanium (HPGE) detector array, and therefore are correlated both spatially and temporally. The combination of emission and transmission data with the ETCT systems allows (1) accurate attenuation correction of the emission data, (2) qualitative correlation of the functional and morphological images, and (3) definition of regions of interest on the x-ray CT images for precise quantification of the radionuclide data. This proposal encompasses 6 specific aims. (1) Corrections will be developed for effects which limit the accuracy and precision of quantitative x-ray and radionuclide data, such photon statistical noise, scatter radiation, and suboptimum placement of energy windows. (2) Reconstruction software will be developed under a subcontract to the University of North Carolina at Chapel Hill (UNC-CH) to improve the quality and quantitative accuracy of the reconstructed images by compensating for nonuniform photon attenuation, scatter radiation, and spatially-variant blurring by the geometric system and scatter response functions. The UNC-CH group will investigate Bayesian algorithms to incorporate a priori information from the x-ray CT image into reconstruction of the radionuclide tomogram. (3) Quantitation of the SPECT image will be improved using the correlated x-ray CT image localization, for attenuation correction, and compensation of partial-volume effects. The effect of noise propagation from the x-ray attenuation map into the SPECT reconstruction will be determined. (4) A gantry will be developed for imaging the canine thorax using the ETCT system. Compensating filters will be added to the x-ray beam path, to improve the signal-to-noise ratio of the attenuation map and to decrease the acquisition time of the radiographic image. (5) A canine model will be used to test the hypothesis that blood-flow measurements using 99mTc-MIBI and ETCT correlates with myocardial perfusion determined with radiolabelled microspheres. (6) Optimal operating configurations of ETCT will be investigated by testing alternative HPGe detectors and and improved detector collimators, leading to a design concept for a clinically usable ETCT system. These studies will evaluate the performance of the ETCT system for quantitative radionuclide studies by theoretical calculations, computer simulations, experimental measurements, and validation in an animal model of myocardial perfusion, with the long-term goal of improving radionuclide assessments of myocardial perfusion, as well as cerebral blood flow, tumor dosimetry, and tumor localization in human patients.